Abstract
Factor XIII (FXIII) is a transglutaminase involved in blood coagulation. The enzyme is activated by thrombin cleaving the peptide bond R37 -G38. A common mutation V34L found in FXIII has been correlated with protection from myocardial infarction. Also FXIII V34L is activated more quickly than the wild type. In the present study, FXIII (28–41) V34L mutant peptide bound to thrombin has been modeled and molecular dynamics simulations were carried out using Insight II. An average structure was calculated after simulation. The structure showed significant difference from the crystal structure of the wild type FXIII (28–37) peptide bound to thrombin. In the crystal structure the peptide adopts a folded conformation in such a way that the hydrophobic side chains of V29 and V34 occupy the apolar binding site of thrombin. The modeled V34L peptide adopts a significantly different conformation and only the bulkier L34 occupies the apolar binding site while V29 side chain is exposed to the bulk solvent. Hence, this may speed up the release of FXIII from thrombin after its activation.
Published Version
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